Abstract
Background2,3,5,4′-tetrahydroxystilbence-2-O-β-D-glucoside (TSG) is a polyhydroxyphenolic compound, which exhibited a broad spectrum of pharmacological activities, such as anti-inflammatory, anti-depression, anti-oxidation and anti-atherosclerosis. However, the compound had poor bioavailability and the underlying absorption mechanisms had not been studied. Therefore, the purpose of this study was to investigate the intestinal absorption mechanism of TSG.MethodsThis study used Caco-2 cell monolayer model and single-pass intestinal perfusion model to explore the gastrointestinal absorption mechanisms of TSG. The effects of basic parameters such as drug concentration, time and pH on the intestinal absorption of TSG were analyzed by high performance liquid chromatography. The absorption susceptibility of TSG to three inhibitors, P-gp inhibitors verapamil hydrochloride and quinidine, and MRP2 inhibitor probenecid were also assessed.ResultsTSG was poorly absorbed in the intestines and the absorption of TSG in stomach is much higher than that in intestine. Both in vitro and in situ experiments showed that the absorption of TSG was saturated with increasing concentration and it was better absorbed in a weakly acidic environment pH 6.4. Moreover, TSG interacts with P-gp and MRP2, and TSG was not only the substrate of the P-gp and MRP2, but also affected the expression of P-gp and MRP2.ConclusionsIt was concluded that the gastrointestinal absorption the most unique active ingredient and considered as the mechanisms of TSG involved processes passive transport and the participation of efflux transporters.
Highlights
Polygonum multiflorum, the dry root of Polygonum multiflorum Thunb. (Polygonaceae), is wildly used as a nourishing Chinese medicine for the remarkable pharmacological effects of neuroprotection, antioxidation, improving immunity, hypolipidemic, antiatherosclerosis [1], anti-liver injury [2] and anti-cancer [3]
Caco-2 cell monolayer model The results of the cytotoxicity test In order to avoid the false positive result of the target drug on the cells, we examined the effect of the target drug on cell viability by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay before the transport experiment
The absorption of TSG on Caco-2 cell monolayer model did not have time-dependent relation which was indicated by the Apparent absorption coefficient (Papp) values obtained after incubation with TSG for 1, 2, 3 and 4 h across Caco-2 cell monolayer (Fig. 3b and Fig. 3c)
Summary
The dry root of Polygonum multiflorum Thunb. (Polygonaceae), is wildly used as a nourishing Chinese medicine for the remarkable pharmacological effects of neuroprotection, antioxidation, improving immunity, hypolipidemic, antiatherosclerosis [1], anti-liver injury [2] and anti-cancer [3]. (Polygonaceae), is wildly used as a nourishing Chinese medicine for the remarkable pharmacological effects of neuroprotection, antioxidation, improving immunity, hypolipidemic, antiatherosclerosis [1], anti-liver injury [2] and anti-cancer [3]. 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) (Fig. 1) is the most unique active ingredient and considered as the quality index of Polygonum multiflorum in the 2015 edition of Chinese pharmacopoeia. Modern studies have shown that TSG has a wide range of pharmacological effects, including anti-inflammatory [4], anti-depression [5], Wang et al BMC Pharmacology and Toxicology (2020) 21:7 transport mechanism of TSG, western blotting was carried out to explore the effect of TSG on P-gp and MRP2 expression during absorption by administering P-gp inhibitors (verapamil hydrochloride and quinidine) and MRP2 inhibitor (probenecid). We hope the study will provide a reference for improving the bioavailability of TSG, designing a reasonable dosing regimen and predicting drug interactions
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